What are the comparative effects and risks of MDMA (3,4-Methylenedioxymethamphetamine) versus cocaine?

Comparative Effects and Risks of MDMA versus Cocaine

Both MDMA and cocaine are associated with increased risk of stroke, cardiovascular complications, and dependence, but cocaine presents a higher overall risk profile with more severe cardiovascular effects and greater reinforcing properties leading to addiction.

Cardiovascular Effects

Cocaine

• Produces a hyperadrenergic state by blocking neuronal reuptake of norepinephrine and dopamine 1
• Causes dramatic increases in heart rate and blood pressure 1
• Induces coronary vasoconstriction while simultaneously increasing myocardial oxygen demand 1
• Associated with higher risk of both ischemic stroke (OR 2.03) and hemorrhagic stroke (OR 2.33) 1
• Can cause myocardial ischemia and infarction even in the absence of obstructive coronary artery disease 1
• Additional hazardous effects include 1:
  • Increased myocardial contractility
  • Cardiac arrhythmias
  • Direct myocardial toxicity
  • Increased platelet aggregability
  • Endothelial dysfunction
  • Hypertensive vascular catastrophes (aortic dissection, cerebrovascular hemorrhage)

MDMA

• Also affects monoaminergic systems but with stronger effects on serotonin compared to cocaine 2
• Associated with increased risk of stroke but with less evidence for direct cardiotoxicity compared to cocaine 1
• Produces hyperactivity and can decrease social contacts in experimental models 2
• May have anxiolytic effects when combined with cocaine, unlike cocaine alone 2

Neurological Effects and Risks

Cocaine

• Higher risk of both ischemic and hemorrhagic stroke compared to MDMA 1
• Cocaine-associated intracranial hemorrhage leads to worse functional outcomes and nearly 3-fold greater risk of death during hospitalization 1
• Amphetamine-like compounds (including cocaine) are associated with ICH (adjusted OR 4.95) 1

MDMA

• Affects serotonergic systems more prominently than dopaminergic systems 2
• Can produce changes in brain monoamines, particularly when combined with cocaine 2
• May have less direct neurotoxicity in acute use compared to cocaine, but chronic use can lead to serotonergic neurotoxicity 1

Addiction Potential

Cocaine

• Higher reinforcing efficacy in experimental models 3
• Higher breaking point in progressive-ratio schedules of reinforcement 3
• Self-administered at more doses compared to MDMA 3

MDMA

• Functions as a reinforcer but with significantly lower peak breaking point than cocaine 3
• Self-administered at fewer doses in experimental models 3
• Can reinstate cocaine-seeking behavior, suggesting cross-sensitization 4
• Low doses of MDMA can enhance the locomotor and conditioned rewarding effects of cocaine 5

Clinical Presentations and Management

Acute Chest Pain

• Chest pain is the most frequent presenting complaint of cocaine abuse 1
• For patients presenting with acute chest pain, it is reasonable to consider both cocaine and methamphetamine (similar to MDMA) as potential causes (Class IIa recommendation) 1
• Frequency of acute coronary syndrome is <10% among stimulant users in most studies 1

Treatment Approaches

• For both substances, the American Academy of Addiction Psychiatry recommends a combination of contingency management plus community reinforcement approach as the most effective treatment 6
• Cognitive Behavioral Therapy helps develop specific behavioral goals and self-monitoring techniques for both types of substance use disorders 6
• Physical activity interventions with at least 90 minutes of moderate to vigorous activity per week are recommended 6
• Brief interventions (5-30 minutes) incorporating individualized feedback show benefit 6

Screening and Assessment

• Single-question screen: "How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?" has high sensitivity (90-100%) 1
• Drug Abuse Screening Test-10 can accurately identify substance abuse and dependence 1
• Urine typically tests positive for cocaine or methamphetamine within 1-4 hours of consumption and continues to test positive for 2-4 days 1

Key Differences

• Cocaine has higher reinforcing properties and addiction potential 3
• Cocaine presents greater cardiovascular risks, particularly for stroke and myocardial infarction 1
• MDMA has stronger effects on serotonergic systems, while cocaine primarily affects dopaminergic systems 2
• Combined use produces a predominance of serotonin over dopamine, associated with an anxiolytic profile but fewer social contacts 2

Recommendations

• Referral to an appropriate therapeutic program is reasonable for patients who abuse either cocaine or MDMA (Class IIa recommendation) 1
• Regular monitoring through objective measures (e.g., urine testing) and ongoing assessment of psychiatric symptoms is essential 6
• Combined treatment approaches yield better results for patient retention and relapse prevention than individual treatments alone 6